SKA3 Expression as a Prognostic Factor for Patients with Pancreatic Adenocarcinoma.

The spindle and kinetochore-associated complex subunit 3 (SKA3) is a protein essential for proper chromosome segregation during mitosis and thus responsible for maintaining genome stability. Although its involvement in the pathogenesis of various cancer types has been reported, the potential clinicopathological significance of SKA3 in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Therefore, this study aimed to assess clinicopathological associations and prognostic value of SKA3 in PDAC. For this purpose, in-house immunohistochemical analysis on tissue macroarrays (TMAs), as well as a bioinformatic examination using publicly available RNA-Seq dataset, were performed. It was demonstrated that SKA3 expression at both mRNA and protein levels was significantly elevated in PDAC compared to control tissues. Upregulated mRNA expression constituted an independent unfavorable prognostic factor for the overall survival of PDAC patients, whereas altered SKA3 protein levels were associated with significantly better clinical outcomes. The last observation was particularly clear in the early-stage tumors. These findings render SKA3 a promising prognostic biomarker for patients with pancreatic ductal adenocarcinoma. However, further studies are needed to confirm this conclusion.

Cyclic AMP but Not Calmodulin as a Potential Wasoconstrictor in Simulated Reperfusion.

The phenomena of ischemia and reperfusion are associated with the pathological background of cardiovascular diseases. Ischemia is initiated by ischemia reperfusion injury (IRI), which involves disruption of intracellular signaling pathways and causes cell death. The aim of this study was to assess the reactivity of vascular smooth muscle cells in the conditions of induced ischemia and reperfusion, and to determine the mechanisms leading to contractility disorders. This study was conducted using classical pharmacometric methods on an isolated model of the rat caudal artery. The experiment consisted of the analysis of the final and initial perfusate pressure measurements after induction of arterial contraction with phenylephrine in the presence of forskolin and A7 hydrochloride, two ligands modifying the contractility of vascular smooth muscle cells (VSMC). The pharmacometric analysis showed that in simulated reperfusion, cyclic nucleotides have a vasoconstrictive effect, and calmodulin has a vasodilating effect. The responsiveness of vascular smooth muscle cells to the vasopressor effects of α1-adrenomimetics during reperfusion may change uncontrollably, and the effects of secondary messengers may be counter physiological. Further studies are needed to evaluate the function of other second messengers on VSMCs in the process of ischemia and reperfusion.

Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

Neuroprotective Properties of Linagliptin: Focus on Biochemical Mechanisms in Cerebral Ischemia, Vascular Dysfunction and Certain Neurodegenerative Diseases.

Linagliptin is a representative of dipeptidyl peptidase 4 (DPP-4) inhibitors which are registered and used effectively in a treatment of diabetes mellitus type 2. They increase the levels of active forms of endogenous incretins such as GLP-1 and GIP by inhibiting their enzymatic decomposition. Scientific reports suggest beneficial effects of linagliptin administration via immunological and biochemical pathways involved in neuroprotective processes of CNS. Linagliptin's administration leads to a decrease in the concentration of proinflammatory factors such as: TNF-α, IL-6 and increases the number of anti-inflammatory patrolling monocytes CX3CR1bright. Significant reduction in Aß42 level has been associated with the use of linagliptin implying potential application in Alzheimer's disease. Linagliptin improved vascular functions by increasing production of nitric oxide (NO) and limiting concentration of apolipoprotein B. Linagliptin-induced decrease in macrophages infiltration may provide improvement in atheromatous plaque stabilization. Premedication with linagliptin increases neuron's survival after stroke and augments neuronal stem cells proliferation. It seems to be connected with SDF-1α/CXCR4 signaling pathway. Linagliptin prevented abnormal proliferation and migration of rat brain microvascular endothelial cells in a state of hypoperfusion via SIRT1/HIF-1α/VEGF pathway. The article presents a summary of the studies assessing neuroprotective properties of linagliptin with special emphasis on cerebral ischemia, vascular dysfunction and neurodegenerative diseases.

Liraglutide and its Neuroprotective Properties-Focus on Possible Biochemical Mechanisms in Alzheimer's Disease and Cerebral Ischemic Events.

Liraglutide is a GLP-1 analog (glucagon like peptide-1) used primarily in the treatment of diabetes mellitus type 2 (DM2) and obesity. The literature starts to suggest that liraglutide may reduce the effects of ischemic stroke by activating anti-apoptotic pathways, as well as limiting the harmful effects of free radicals. The GLP-1R expression has been reported in the cerebral cortex, especially occipital and frontal lobes, the hypothalamus, and the thalamus. Liraglutide reduced the area of ischemia caused by MCAO (middle cerebral artery occlusion), limited neurological deficits, decreased hyperglycemia caused by stress, and presented anti-apoptotic effects by increasing the expression of Bcl-2 and Bcl-xl proteins and reduction of Bax and Bad protein expression. The pharmaceutical managed to decrease concentrations of proapoptotic factors, such as NF-κB (Nuclear Factor-kappa ß), ICAM-1 (Intercellular Adhesion Molecule 1), caspase-3, and reduced the level of TUNEL-positive cells. Liraglutide was able to reduce the level of free radicals by decreasing the level of malondialdehyde (MDA), and increasing the superoxide dismutase level (SOD), glutathione (GSH), and catalase. Liraglutide may affect the neurovascular unit causing its remodeling, which seems to be crucial for recovery after stroke. Liraglutide may stabilize atherosclerotic plaque, as well as counteract its early formation and further development. Liraglutide, through its binding to GLP-1R (glucagon like peptide-1 receptor) and consequent activation of PI3K/MAPK (Phosphoinositide 3-kinase/mitogen associated protein kinase) dependent pathways, may have a positive impact on Aß (amyloid beta) trafficking and clearance by increasing the presence of Aß transporters in cerebrospinal fluid. Liraglutide seems to affect tau pathology. It is possible that liraglutide may have some stem cell stimulating properties. The effects may be connected with PKA (phosphorylase kinase A) activation. This paper presents potential mechanisms of liraglutide activity in conditions connected with neuronal damage, with special emphasis on Alzheimer's disease and cerebral ischemia.

Improved imaging of colorectal liver metastases using single-source, fast kVp-switching, dual-energy CT: preliminary results.

PURPOSE: Computed tomography remains the first-choice modality for assessment of colorectal cancer liver metastases (CRLM). Dual-energy computed tomography (DECT) is a relatively new technique that is becoming increasingly available. One of the advantages of DECT is the ability to maximise iodine detection. Our aim was to test whether single-source, fast kVp-switching DECT can improve imaging quality of CRLM compared to conventional (polychromatic) CT. MATERIAL AND METHODS: Twenty consecutive patients were enrolled into a preliminary prospective study. The scanning protocol consisted of four phases: non-contrast with standard 120 kV tube voltage and three post-contrast phases with rapid voltage switching. As a result, three sets of images were reconstructed: pre- and postcontrast polychromatic (PR), monochromatic (MR), and iodine concentration map (IM). To compare the sensitivity of the tested reconstructions, the number of CRLMs and the maximum diameter of the largest lesion were calculated. Objective image quality was measured as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The radiation dose was expressed as CTDIvol. RESULTS: Imaging was successfully performed in all patients. The number of detected lesions was significantly lower on PR images than on IM and MR 50-70 keV (mean number: 4.20 and 4.45, respectively). IM and MR at 70 keV presented the highest quality. SNR was significantly higher for IM and 70 keV images than for other reconstructions. The mean radiation dose was 14.61 mGy for non-contrast 120 kV scan and 17.89 mGy for single DECT scan (p < 0.05). CONCLUSIONS: DECT is a promising tool for CRLM imaging. IM and low-photon energy MR present the highest differences in contrast between metastases and the normal liver parenchyma.

Noninvasive evaluation of renal tissue oxygenation with blood oxygen level-dependent magnetic resonance imaging early after transplantation has a limited predictive value for the delayed graft function.

PURPOSE: The aim of this study was to evaluate the feasibility of renal oxygenation assessment using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the early period after kidney transplantation and to estimate its prognostic value for delayed graft function. MATERIAL AND METHODS: Examinations were performed in 50 subjects: 40 patients within a week after the kidney transplantation and 10 healthy controls, using T2*-weighted sequence. Measurements in transplant patients were correlated to basic laboratory parameters in the early period after transplantation and at follow-up. RESULTS: Examinations of seven patients (18%) were rejected due to their poor technical quality. Mean R2* values in transplant recipients were lower than in controls (11.6 vs. 15.9 Hz; p = 0.0001). An R2* value of 0.28 Hz was calculated as the minimal detectable change. There was no relation between R2* values and laboratory parameters. However, patients eGFR ≥ 40 ml/min/1.73 m2 presented higher R2* values than recipients eGFR < 40 ml/min/1.73 m2 (12.0 vs. 11.1 Hz; p = 0.0189). In ROC analysis R2* of ≤ 11.7 predicted an early reduced graft function with 0.82 sensitivity and 56% specificity (AUC = 0.708; p = 0.024) but was not useful for delayed graft function prediction (p > 0.7). CONCLUSIONS: Evaluation of renal graft oxygenation using BOLD MRI is technically challenging in the early period after transplantation. An R2* value of 0.28 Hz may in practice be considered as the minimal detectable change. The delayed graft function seems not to be dependent on early oxygenation values. Further, large-scale studies are necessary to confirm the latter observation.

Surgical treatment of recurrent urachal carcinoma with liver metastasis: a case report and literature review.

BACKGROUND: Urachal carcinoma is a rare malignancy with poor prognosis due to late presentation of the disease and its aggressiveness. Surgery remains the mainstay of therapy even in cases of disease recurrence. To the best of our knowledge, this is the first report of salvage surgery in the case of urachal carcinoma with liver metastasis. CASE PRESENTATION: The patient was a young woman who suffered from locally advanced urachal carcinoma treated with en-bloc cystectomy, hysterectomy with bilateral adnexectomy, partial resection of the sigmoid colon, and partial resection of the rectus abdominis muscle with the fascia, skin, and umbilicus. Adjuvant chemotherapy with paclitaxel and carboplatin was applied. Two years after the treatment, she was diagnosed with a single liver metastasis and a local pelvic recurrence. In a two-step operation, the patient underwent right hemihepatectomy as well as resection of pelvic recurrence site and adjuvant chemotherapy with gemcitabine. Due to the disease progression, a complete resection of the lesions was not achieved and the response to chemotherapy was poor. The patient died of the disease after a year. CONCLUSIONS: Surgery is the first line of treatment for urachal carcinoma and should be always considered as an option in cases of disease recurrence. Radical initial surgical management, close patient surveillance, and prompt treatment of disease relapse may all contribute to prolonging patient's survival.

Rho-kinase inhibitor reduces hypersensitivity to ANG II in human mesenteric arteries retrieved and conserved under the same conditions as transplanted organs.

Rho-kinase and GTP-ase Rho are important regulators of vascular tone and blood pressure. The aim of this study was to investigate the role of Rho-kinase in artery reactions induced by angiotensin II (ANG II) and the effects of ischemia-reperfusion injury as well as the function of intra- and extracellular calcium in these reactions. Experiments were performed on mesenteric superior arteries procured from cadaveric organ donors and conserved under the same conditions as transplanted kidneys. The vascular contraction in reaction to ANG II was measured in the presence of Rho-kinase inhibitor Y-27632, after ischemia and reperfusion, in Ca2+ and Ca2+-free solution. The maximal response to ANG II was reduced after ischemia, while an increase was observed after reperfusion. Vascular contraction induced by ANG II was decreased by Y-27632. Y-27632 reduced vascular contraction after reperfusion, both in Ca2+ and Ca2+-free solution. Reperfusion augments vascular contraction in reaction to ANG II. The Rho-kinase inhibitor Y-27632 reduces the hypersensitivity to ANG II after reperfusion mediated by both intra- and extracellular calcium. These results confirm the role of Rho-kinase in receptor-independent function of ANG II and in reperfusion-induced hypersensitivity.

The Use of Cannabidiol in Metabolic Syndrome-An Opportunity to Improve the Patient's Health or Much Ado about Nothing?

Cannabis-derived therapies are gaining popularity in the medical world. More and more perfect forms of cannabinoids are sought, which could be used in the treatment of many common diseases, including metabolic syndrome, whose occurrence is also increasing. The purpose of this review was to investigate the usefulness of cannabinoids, mainly cannabidiol (CBD), in individuals with obesity, impaired glucose and lipid metabolism, high blood pressure, and non-alcoholic fatty liver disease (NAFLD). We summarised the most recent research on the broad topic of cannabis-derived influence on metabolic syndrome components. Since there is a lot of work on the effects of Δ9-THC (Δ9-tetrahydrocannabinol) on metabolism and far less on cannabidiol, we felt it needed to be sorted out and summarised in this review. The research results on the use of cannabidiol in obesity are contraindicatory. When it comes to glucose homeostasis, it appears that CBD maintains it, sensitises adipose tissue to insulin, and reduces fasting glucose levels, so it seems to be a potential target in this kind of metabolic disorder, but some research results are inconclusive. CBD shows some promising results in the treatment of various lipid disorders. Some studies have proven its positive effect by decreasing LDL and increasing HDL as well. Despite their probable efficacy, CBD and its derivatives will likely remain an adjunctive treatment rather than a mainstay of therapy. Studies have also shown that CBD in patients with hypertension has positive effects, even though the hypotensive properties of cannabidiol are small. However, CBD can be used to prevent blood pressure surges, stabilise them, and have a protective effect on blood vessels. Results from preclinical studies have shown that the effect of cannabidiol on NAFLD may be potentially beneficial in the treatment of the metabolic syndrome and its components. Nevertheless, there is limited data on CBD and NAFLD in human studies. Because of the numerous confounding factors, the conclusions are unclear, and more research in this field is required.

Does Intense Endurance Workout Have an Impact on Serum Levels of Sex Hormones in Males?

The benefits of physical activity and sports are widely known and proved to be crucial for overall health and well-being. In this research, the authors decided to measure the impact of endurance training in a professional male rowing team on the serum concentration levels of testosterone, estradiol, sex hormone binding globulin (SHBG) and nitric oxide (NO) and apolipoprotein A1 (Apo-A1). Proper levels of the serum concentration are necessary in order to maintain physical effectiveness. Authors analyzed the data and reviewed the former conterminous articles to find the possible mechanisms leading to changes of serum concentration of certain hormones and molecules. The direct effect of physical activity was a decrease in testosterone serum concentration (from 7.12 ± 0.4 to 6.59 ± 0.35 (ng/mL)), sex hormone binding globulin serum concentration (from 39.50 ± 2.48 to 34.27 ± 2.33 (nmol/L)), nitric oxide serum concentration (from 440.21 ± 88.64 to 432 ± 91.89 (ng/mL)), increase in estradiol serum concentration (from 78.2 ± 11.21 to 83.01 ± 13.21 (pg/mL)) and no significant increase in Apo-A1 serum concentration (from 2.63 ± 0.2 to 2.69 ± 0.21 (mg/mL)). Low testosterone concentration in OTS may be a consequence of increased conversion to estradiol, because gonadotropic stimulation is maintained. Apo-A1 serum concentration was measured due to a strong connection with testosterone level and its possible impact of decreasing cardiovascular risk.

Vitamin D Supplementation and Its Impact on Different Types of Bone Fractures.

Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures that occur at specific ages and due to different circumstances, the influence of vitamin D on the frequency of a particular fracture may differ. Thus, the authors investigated the possible preventive effect of vitamin D on the risks of vertebral fractures, hip fractures, stress fractures and pediatric fractures. Additional aspects of vitamin D, especially on recuperation after injures and its impact on the severity of particular fractures, were also discussed. It was suggested that vitamin D supplementation may contribute to a reduction in hip fracture risk due to reduced bone turnover, decreased frequency of falls and improved muscle function. Furthermore, vitamin D appears to lower the risk of stress fractures in athletes and military recruits. Due to a nonunified protocol design, presented investigations show inconsistencies between vitamin D supplementation and a decreased risk of vertebral fractures. However, a vitamin D preventive effect on pediatric fractures seems to be implausible.

Hepatorenal Syndrome and Other Post-Liver Transplantation Complications: Case Studies and Literature Review.

Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis.

ABSTRACT: The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.

Effects of Energy Drink Consumption on Physical Performance and Potential Danger of Inordinate Usage.

The rise in energy drink (ED) intake in the general population and athletes has been achieved with smart and effective marketing strategies. There is a robust base of evidence showing that adolescents are the main consumers of EDs. The prevalence of ED usage in this group ranges from 52% to 68%, whilst in adults is estimated at 32%. The compositions of EDs vary widely. Caffeine content can range from 75 to 240 mg, whereas the average taurine quantity is 342.28 mg/100 mL. Unfortunately, exact amounts of the other ED elements are often not disclosed by manufacturers. Caffeine and taurine in doses 3-6 mg/kg and 1-6 g, respectively, appear to be the main ergogenic elements. However, additive or synergic properties between them seem to be implausible. Because of non-unified protocol design, presented studies show inconsistency between ED ingestion and improved physical performance. Potential side effects caused by abusive consumption or missed contraindications are the aspects that are the most often overlooked by consumers and not fully elucidated by ED producers. In this review, the authors aimed to present the latest scientific information on ED components and their possible impact on improving physical performance as well as to bring emphasis to the danger of inordinate consumption.

Evidence-Based Aerobic Exercise Training in Metabolic-Associated Fatty Liver Disease: Systematic Review with Meta-Analysis.

BACKGROUND: This meta-analysis evaluates the overall effect of the non-pharmacological intervention, aerobic exercise, upon serum liver enzymes levels, glucose metabolism and anthropometric measures amongst patients with metabolic associated fatty liver disease (MAFLD). It also examines whether the effects on these outcomes are moderated by the aerobic training protocol when considered according to the American College of Sports Medicine (ACSM) recommended FITT (frequency, intensity, time, type) principles. Approach and Results: Fifteen randomized control trials were included in the meta-analysis. Compared with usual care, continuous and interval training showed significant efficacy in alanine aminotransferase (ALT) level improvement (MD = -2.4, 95% CI: -4.34 to -0.46 p = 0.015, I2 = 9.1%). Interventions based on all types of aerobic exercise protocols showed significant improvement of intrahepatic triglycerides (MD = -4.0557, 95% CI: -5.3711 to -2.7403, p < 0.0001, I2 = 0%) and BMI (MD = -0.9774, 95% CI: -1.4086 to -0.5462, p < 0.0001, I2 = 0). Meta-regression analysis demonstrated a significant correlation between total intervention time and ALT level (for all aerobic protocols: 6.0056, se = 2.6896, z = 2.2329, p = 0.02; as well as for continuous and interval aerobic protocols: 5.5069, se = 2.7315, z = 2.016, p = 0.04). CONCLUSIONS: All types of aerobic exercise protocols are effective at improving intrahepatic triglycerides and lead to a reduction in body mass index. In addition, continuous and interval aerobic exercise may be more effective at improving ALT ≤12 weeks intervention time benefits the management of MAFLD.

The role of calcium in modulating the reactivity of the smooth muscle cells during ischemia/reperfusion. Part 1.

BACKGROUND: Calcium ions regulate the function of cells in many ways, acting as first messengers of intercellular information and second messengers of intracellular information. Changes in cytoplasmic calcium levels depend on calcium influx from the extracellular space or calcium release from cellular stores. Increase in calcium ion concentration takes place in pathological situations, such as ischemia. In the present study the roles of calcium and G protein in contraction induced by angiotensin II (agonist of the metabotropic receptor AT1), phenylephrine (agonist of alpha1-adrenergic metabotropic receptor), and Bay K8644 (a calcium channel agonist) after ischemia/reperfusion were investigated. MATERIAL/METHODS: Experiments were performed on perfused male Wistar rats' tail arteries. Contraction induced by angiotensin II, phenylephrine, and Bay K8644 mediated by intracellular or extracellular calcium after ischemia/reperfusion and in the presence of the blocker of G protein Bordetella pertussis toxin (P 7208) was analyzed. RESULTS: Ischemia reduced while reperfusion augmented the response of vascular smooth muscle cells to angiotensin II and phenylephrine, but they did not change the effects of Bay K8644. P 7208 decreased the effects of phenylephrine mediated by intracellular and extracellular calcium and reduced the reactions of angiotensin II mediated only by intracellular calcium, but did not change the effects of Bay K8644. CONCLUSIONS: Ischemia/reperfusion modulates vascular contraction induced by angiotensin II and phenylephrine. Both intracellular and extracellular calcium ions mediate the contraction induced by angiotensin II and phenylephrine. The results suggests that G protein modulates the effects of angiotensin II mediated by intracellular calcium ions while it plays a role in the reactions of phenylephrine mediated by calcium coming from both sources, intracellular and extracellular.

The role of calcium in modulating the reactivity of the smooth muscle cells during ischemia/reperfusion. Part 2.

BACKGROUND: Damage of transplanted organs during reperfusion is still a problem that prompts the search for new drugs able to diminish the risk of graft rejection. The aim of this study was to examine the influence of antioxidant system on the contraction of arteries induced by angiotensin II during ischemia/reperfusion and to determine the role of intracellular and extracellular calcium ions under these conditions. MATERIAL/METHODS: The experiments were performed on male Wistar rats' tail arteries. The effects of angiotensin II on vascular tone were examined after ischemia/reperfusion in the presence of catalase or aminotriazole. To determine the role of intracellular and extracellular Ca(2+), the experiments were performed in Ca(2+)-free PSS and PSS. RESULTS: Angiotensin II increased perfusion pressure in both Ca(2+)-free PSS and PSS. After ischemia, the reactions induced by angiotensin II were lower, while after reperfusion they were higher. In the presence of catalase the effects induced by angiotensin II were lower and in the presence of aminotriazole higher. CONCLUSIONS: Ischemia inhibits and reperfusion augments the perfusion pressure induced by angiotensin II. The results confirm the vasoprotective effect of catalase and the destructive influence of aminotriazole in modulating the reactions of vascular smooth muscle cells to ANG II after ischemia/reperfusion. These results suggest that the antioxidant system plays a role in modulating the reactions induced by angiotensin II after ischemia/reperfusion and that reperfusion disturbs the balance between antioxidants and the production of reactive oxygen species.

Long-term results of simultaneous and delayed liver resections of synchronous colorectal cancer liver metastases.

BACKGROUND: Complete resection is the only potential curative treatment of synchronous colorectal liver metastases. Although simultaneous liver and colon resections became an accepted procedure at specialized centres for selected patients, there is still little data about the long-term results of simultaneous operative procedures compared with those of delayed operations. In this retrospective study, the long-term survival rates of the patients who underwent simultaneous or delayed resections were presented. METHODS: A retrospective analysis of liver resections in our institution between 1997 and 2012 was performed. Among 131 patients presented with synchronous colorectal liver metastases, 52 underwent simultaneous and 79 delayed resection. Patients with extrahepatic metastases were excluded, except for 10 patients with metastases limited to liver and lungs that were qualified as resectable. RESULTS: Age, sex and localization of the primary tumour were similar in the two groups. In the delayed resection group, the majority of colon resections were performed in different hospitals. The frequency of complications did not differ between the groups. The 1, 5 and 10 years survival rates were 77%, 43% and 20% in simultaneous and 86%, 37% and 19% in delayed resection group, respectively. No cancer related deaths occurred after more than 10 years of observation. CONCLUSION: The long-term outcome of simultaneous resection of synchronous colorectal liver metastases is comparable to delayed resection.

An unusual case of a tuberculous granuloma of the liver presenting thirteen years after intravesical BCG - therapy for bladder cancer.

The authors present the case of a female patient with a tumor of segment VII of the liver, which was postoperatively identified as a tuberculous granuloma. The patient was admitted for elective surgery for a liver tumor, which had been diagnosed a few months before. Computed tomography and nuclear magnetic resonance were performed, based on which focal nodular hyperplasia was suspected. Thirteen years prior to admission the patient had undergone a transurethral resection of superficial bladder carcinoma, followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG-therapy). Upon surgery, segment VII of the liver was resected; postoperative course was uneventful. After the identification of granuloma, the patient was referred to a phthysiatric clinic for further diagnostics and treatment. The authors have deemed this case worthy of reporting primarily due to the exceptionally long period between the completion of BCG therapy and the onset of hepatic tumor.